2,2-Difluoro-13,14 didehydro-PGF1 compounds

ABSTRACT

This invention comprises certain analogs of the prostaglandins in which the double bond between C-13 and C-14 is replaced by a triple bond. Also provided in this invention, are novel chemical processes and novel chemical intermediates useful in the preparation of the above prostaglandin analogs. These prostaglandin analogs exhibit prostaglandin-like activity, and are accordingly useful for the same pharmacological purposes as the prostaglandins. Among these purposes are blood pressure lowering, labor induction at term, reproductive-cycle regulation, gastric antisecretory action, and the like.

The present application is a divisional application of Ser. No. 657,739,filed Feb. 13, 1976, now U.S. Pat. No. 4,029,681.

The present invention relates to prostaglandin analogs, for which theessential material constituting disclosure therefor is incorporated byreference here from Ser. No. 657,739, filed Feb. 13, 1976, now pendingissuance as a United States Patent.

I claim:
 1. A prostaglandin analog of the formula: ##STR1## wherein D is##STR2## wherein Y₁ is --C.tbd.C--; wherein g is one, two, or 3;Whereinm is one to 5, inclusive; Wherein M₁ is ##STR3## wherein R₅ and R₆ arehydrogen or methyl, with the proviso that one of R₅ and R₆ is methylonly when the other is hydrogen; Wherein L₁ is ##STR4## wherein R₃ andR₄ are hydrogen, methyl, or fluoro, being the same or different, withthe proviso that one of R₃ and R₄ is fluoro only when the other ishydrogen or fluoro; Wherein R₁ is hydrogen, alkyl of one to 12 carbonatoms, inclusive, cycloalkyl of 3 to 10 carbon atoms, inclusive, aralkylof 7 to 12 carbon atoms, inclusive, phenyl, phenyl substituted with one,two, or three chloro or alkyl of one to 3 carbon atoms, inclusive, or apharmacologically acceptable cation.
 2. A compound according to claim 1,wherein D is ##STR5##
 3. A compound according to claim 2, wherein M₁ is##STR6##
 4. A compound according to claim 3, wherein g is one.
 5. Acompound according to claim 4, wherein R₃, R₄, R₅, and R₆ are allhydrogen.
 6. A compound according to claim 2, wherein M₁ is ##STR7## 7.A compound according to claim 6, wherein g is three.
 8. A compoundaccording to claim 6, wherein g is one.
 9. A compound according to claim8, wherein R₃ and R₄ are both hydrogen.
 10. A compound according toclaim 9, wherein R₅ is methyl.
 11. A compound according to claim 9,wherein R₆ is methyl.
 12. 2,2-Difluoro-13,14-didehydro-8β,12α-PGF₁ α,15-methyl ether, a compound according to claim
 11. 13.2,2-Difluoro-13,14 -didehydro-8β,12α-PGF₁ α, methyl ester, 15-methylether, a compound according to claim
 11. 14. A compound according toclaim 9, wherein R₅ and R₆ are both hydrogen. 15.2,2-Difluoro-13,14-didehydro-8β,12α-PGF₁ α, a compound according toclaim
 14. 16. 2,2-Difluoro-13,14-didehydro-8β,12α-PGF₁ α, methyl ester,a compound according to claim
 14. 17. A compound according to claim 8,wherein at least one of R₃ and R₄ is methyl.
 18. A compound according toclaim 17, wherein R₃ and R₄ are both methyl.
 19. A compound according toclaim 18, wherein R₅ is methyl. 20.2,2-Difluoro-15,16,16-trimethyl-13,14-didehydro-8β,12.alpha.-PGF₁ α,methyl ester, a compound according to claim
 19. 21. A compound accordingto claim 18, wherein R₆ is methyl. 22.2,2-Difluoro-16,16-dimethyl-13,14-didehydro-8β,12α-PGF₁ α, methyl ester,15-methyl ether, a compound according to claim
 21. 23. A compoundaccording to claim 18, wherein R₅ and R₆ are both hydrogen. 24.2,2-Difluoro-16,16-dimethyl-13,14-didehydro-8β,12α-PGF₁ α, a compoundaccording to claim
 23. 25.2,2-Difluoro-16,16-dimethyl-13,14-didehydro-8β,12α-PGF₁ α, methyl ester,a compound according to claim
 23. 26. A compound according to claim 8,wherein at least one of R₃ and R₄ is fluoro.
 27. A compound according toclaim 26, wherein R₃ and R₄ are both fluoro.
 28. A compound according toclaim 27, wherein R₅ is methyl. 29.2,2-Difluoro-15-methyl-16,16-difluoro-13,14-didehydro-8β,12α-PGF₁ α,methyl ester, a compound according to claim
 28. 30. A compound accordingto claim 27, wherein R₆ is methyl. 31.2,2-Difluoro-16,16-difluoro-13,14-didehydro-8β,12α-PGF₁ α, methyl ester,15-methyl ether, a compound according to claim
 30. 32. A compoundaccording to claim 27, wherein R₅ and R₆ are both hydrogen. 33.2,2-Difluoro-16,16-difluoro-13,14-didehydro-8β,12α-PGF₁ α, a compoundaccording to claim
 32. 34.2,2-Difluoro-16,16-difluoro-13,14-didehydro-8β,12α-PGF₁ α, methyl ester,a compound according to claim
 32. 35. A compound according to claim 1,wherein D is ##STR8##
 36. A compound according to claim 35, wherein M₁is ##STR9##
 37. A compound according to claim 36, wherein g is one. 38.A compound according to claim 37, wherein R₃, R₄, R₅, and R₆ are allhydrogen.
 39. A compound according to claim 35, wherein M₁ is ##STR10##40. A compound according to claim 39, wherein g is three.
 41. A compoundaccording to claim 39, wherein g is one.
 42. A compound according toclaim 41, wherein R₃ and R₄ are both hydrogen.
 43. A compound accordingto claim 42, wherein R₅ is methyl.
 44. A compound according to claim 42,wherein R₆ is methyl.
 45. 2,2-Difluoro-13,14-didehydro-PGF₁ α, 15-methylether, a compound according to claim
 44. 46.2,2-Difluoro-13,14-didehydro-PGF₁ α, methyl ester, 15-methyl ether, acompound according to claim
 44. 47. A compound according to claim 42,wherein R₅ and R₆ are both hydrogen. 48.2,2-Difluoro-13,14-didehydro-PGF₁ α, a compound according to claim 47.49. 2,2-Difluoro-13,14-didehydro-PGF₁ α, methyl ester, a compoundaccording to claim
 47. 50. A compound according to claim 41, wherein atleast one of R₃ and R₄ is methyl.
 51. A compound according to claim 50,wherein R₃ and R₄ are both methyl.
 52. A compound according to claim 51,wherein R₅ is methyl. 53.2,2-Difluoro-15,16,16-trimethyl-13,14-didehydro-PGF₁ α, methyl ester, acompound according to claim
 52. 54. A compound according to claim 51,wherein R₆ is methyl. 55.2,2-Difluoro-16,16-dimethyl-13,14-didehydro-PGF₁ α, methyl ester,15-methyl ether, a compound according to claim
 54. 56. A compoundaccording to claim 51, wherein R₅ and R₆ are both hydrogen. 57.2,2-Difluoro-16,16-dimethyl-13,14-didehydro-PGF₁ α, a compound accordingto claim
 56. 58. 2,2-Difluoro-16,16-dimethyl-13,14-didehydro-PGF₁ α,methyl ester, a compound according to claim
 56. 59. A compound accordingto claim 41, wherein at least one of R₃ and R₄ is fluoro.
 60. A compoundaccording to claim 59, wherein R₃ and R₄ are both fluoro.
 61. A compoundaccording to claim 60, wherein R₅ is methyl. 62.2,2-Difluoro-15-methyl-16,16-difluoro-13,14-didehydro-PGF₁ α, methylester, a compound according to claim
 61. 63. A compound according toclaim 60, wherein R₆ is methyl. 64.2,2-Difluoro-16,16-difluoro-13,14-didehydro-PGF₁ α, methyl ester,15-methyl ether, a compound according to claim
 63. 65. A compoundaccording to claim 60, wherein R₅ and R₆ are both hydrogen. 66.2,2-Difluoro-16,16-difluoro-13,14-didehydro-PGF₁ α, a compound accordingto claim
 65. 67. 2,2-Difluoro-16,16-difluoro-13,14-didehydro-PGF₁ α,methyl ester, a compound according to claim 65.